The Effects of Mindfulness-Based Interventions in People with Parkinson's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: To examine the effectiveness of mindfulness-based interventions (MBIs) on psychological symptoms, motor symptoms, and quality of life in patients with Parkinson's disease (PD). METHODS: Published studies in Chinese and English languages, conducted from inception to March 2023, were identified by searching PubMed, Web of Science, Cochrane Library, CINAHL, PsycINFO, and two Chinese electronic databases. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. RESULTS: Twelve studies were selected for quantitative syntheses. The impact of MBIs on reducing depression and anxiety, and improving mindfulness and quality of life in PD patients was statistically significant compared to the control group. However, no statistically significant effect on motor symptoms was observed. Subgroup analysis indicated that participants from Asia, those who received face-to-face sessions, and those whose sessions lasted 1.5 hours showed a more positive effect than other subgroups. CONCLUSIONS: Patients with PD may benefit from MBIs to improve psychological symptoms and quality of life. MBIs represent a pivotal non-pharmacological therapeutic approach in clinical practice. CLINICAL IMPLICATIONS: MBIs confer positive improvements in psychological well-being and quality of life in PD patients. However, it remains challenging to conclusively determine their efficacy in addressing motor symptoms.

Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic ß cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.

Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis.

BACKGROUND: Mulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have not been totally clarified. The study aimed to explore the mechanism of mulberry leaf in the treatment of T2DM through tandem mass tag (TMT)-based quantitative proteomics analysis of skeletal muscle. METHODS: The anti-diabetic activity of mulberry leaf extract (MLE) was evaluated by using streptozotocin-induced diabetic rats at a dose of 4.0 g crude drug /kg p.o. daily for 8 weeks. Fasting blood glucose, body weight, food and water intake were monitored at specific intervals, and oral glucose tolerance test and insulin tolerance test were conducted at the 7th and 8th week respectively. At the end of the experiment, levels of glycated hemoglobin A1c, insulin, free fat acid, leptin, adiponectin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assessed and the pathological changes of rat skeletal muscle were observed by HE staining. TMT-based quantitative proteomic analysis of skeletal muscle and bioinformatics analysis were performed and differentially expressed proteins (DEPs) were validated by western blot. The interactions between the components of MLE and DEPs were further assessed using molecular docking. RESULTS: After 8 weeks of MLE intervention, the clinical indications of T2DM such as body weight, food and water intake of rats were improved to a certain extent, while insulin sensitivity was increased and glycemic control was improved. Serum lipid profiles were significantly reduced, and the skeletal muscle fiber gap and atrophy were alleviated. Proteomic analysis of skeletal muscle showed that MLE treatment reversed 19 DEPs in T2DM rats, regulated cholesterol metabolism, fat digestion and absorption, vitamin digestion and absorption and ferroptosis signaling pathways. Key differential proteins Apolipoprotein A-1 (ApoA1) and ApoA4 were successfully validated by western blot and exhibited strong binding activity to the MLE's ingredients. CONCLUSIONS: This study first provided skeletal muscle proteomic changes in T2DM rats before and after MLE treatment, which may help us understand the molecular mechanisms, and provide a foundation for developing potential therapeutic targets of anti-T2DM of MLE.

Mulberry Leaf Flavonoids Inhibit Liver Inflammation in Type 2 Diabetes Rats by Regulating TLR4/MyD88/NF-κB Signaling Pathway.

The incidence of liver-related complications in type 2 diabetes mellitus (T2DM) is rapidly increasing, which affects the physical and mental health of T2DM patients. Mulberry leaf flavonoids (MLF) were confirmed to have certain effects on lowering blood glucose and anti-inflammation. In this study, the high-fat diet (HFD) + STZ method was used to establish T2DM rat model and the MLF was administered by gavage for eight weeks. During the experiment, body weight and blood glucose level were measured at different time points. The pathological changes of rat liver were observed by H&E staining. The serum glucolipid metabolic indicators of serum, fasting insulin (FINS), and inflammatory factors levels were detected by ELISA. The expression levels of toll-like receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα, and nuclear factor kappa-B (NF-κB)/p65 protein in liver tissue were measured by Western Blot. After 8 weeks' MLF treatment, the blood glucose of rats showed a downward trend; glycolipid metabolism level and insulin resistance were improved, which suggested that MLF could improve the disorder of glucose and lipid metabolism. The pathological damage and inflammation of the liver in T2DM rats were significantly improved, the levels of related serum inflammatory factors were reduced, and the expression of liver tissue-related proteins was downregulated. Our results indicated that MLF could reduce blood glucose and inhibit the development of liver inflammation. The mechanisms may be associated with the activation of TLR4/MyD88/NF-κB signal pathway to reduce the levels of inflammatory factors in serum.

Rutin-activated adipose tissue thermogenesis is correlated with increased intestinal short-chain fatty acid levels.

The activation of thermogenic programs in brown adipose tissue (BAT) and white adipose tissue (WAT) provides a promising approach to increasing energy expenditure during obesity and diabetes treatment. Although evidence has been found that rutin activates BAT against obesity and type 2 diabetes mellitus (T2DM), its potential mechanism is not completely understood. In this study, we focused on the potential modulating effect of rutin on short-chain fatty acids (SCFAs) and the thermogenesis of BAT and WAT, aiming to elucidate the molecular mechanism of rutin in the treatment of obesity and T2DM. The results showed that rutin could significantly reduce the body weight and fasting blood glucose, inhibit fat accumulation, relieve hepatic steatosis and ameliorate the disorder of glycolipid metabolism in db/db mice. Moreover, rutin also increased the expression of uncoupling protein 1 (Ucp1) and other thermogenic genes and proteins in BAT and inguinal WAT (IWAT), indicating that rutin activated BAT and induced browning of IWAT. Importantly, rutin markedly enhanced the concentration of SCFAs (acetate, propionate and butyrate) and SCFA-producing enzymes (acetate kinase (ACK), methylmalonyl-CoA decarboxylase (MMD) and butyryl-CoA (BUT)) in feces of db/db mice. In addition, rutin significantly increased the mRNA expression of monocarboxylate transporter 1 (Mct1), catabolic enzyme acyl-CoA medium-chain synthetase 3 (Acsm3), carnitine palmitoyl transferase 1α (Cpt-1α) and Cpt-1ß genes in BAT and IWAT of db/db mice, which is conducive to inducing adipocyte thermogenesis. In summary, our findings revealed that rutin played a variety of regulatory roles in improving glucose and lipid metabolism disorders, reducing hepatic steatosis, inducing browning of IWAT and activating BAT, which has potential therapeutic significance for the treatment of obesity and T2DM. Mechanistically, rutin activates the thermogenesis of BAT and IWAT, which may be associated with increasing the concentration of SCFAs.

Mulberry leaf activates brown adipose tissue and induces browning of inguinal white adipose tissue in type 2 diabetic rats through regulating AMP-activated protein kinase signalling pathway.

The current epidemic of type 2 diabetes mellitus (T2DM) significantly affects human health worldwide. Activation of brown adipocytes and browning of white adipocytes are considered as a promising molecular target for T2DM treatment. Mulberry leaf, a traditional Chinese medicine, has been demonstrated to have multi-biological activities, including anti-diabetic and anti-inflammatory effects. Our experimental results showed that mulberry leaf significantly alleviated the disorder of glucose and lipid metabolism in T2DM rats. In addition, mulberry leaf induced browning of inguinal white adipose tissue (IWAT) by enhancing the expressions of brown-mark genes as well as beige-specific genes, including uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), PRD1-BF-1-RIZ1 homologous domain containing protein 16 (PRDM16), cell death inducing DFFA-like effector A (Cidea), CD137 and transmembrane protein 26 (TMEM26). Mulberry leaf also activated brown adipose tissue (BAT) by increasing the expressions of brown-mark genes including UCP1, PGC-1α, PPARα, PRDM16 and Cidea. Moreover, mulberry leaf enhanced the expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) genes that are responsible for mitochondrial biogenesis in IWAT and BAT. Importantly, mulberry leaf also increased the expression of UCP1 and carnitine palmitoyl transferase 1 (CPT-1) proteins in both IWAT and BAT via a mechanism involving AMP-activated protein kinase (AMPK) and PGC-1α pathway. In conclusion, our findings identify the role of mulberry leaf in inducing adipose browning, indicating that mulberry leaf may be used as a candidate browning agent for the treatment of T2DM.

The effect and pharmacology of Yizhi Sheng Hui decoction on Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) has gradually increased as society has aged and is now a serious social problem. In the clinical treatment of AD, patients show improvement in cognitive function after treatment with the traditional Chinese medicine compound, Yizhi Sheng Hui (YZSH) decoction. This study systematically investigates the effect and pharmacology of the YZSH decoction on AD. METHODS: In this study, 24 SAMP8 AD model mice were randomly divided into three groups: an untreated control group, a group treated with the YZSH decoction, and a positive control group treated with donepezil hydrochloride. Eight SAMR1 mice were placed in the normal control group. A Morris water maze test and a step-down test were conducted at 8 and 13 weeks after continuous intragastric administration of the two drugs. After 13 weeks of administration, the hippocampal expression of Aß1-42 and tau protein were measured. RESULTS: There was no change in the latent period duration and the number of platform crossings in each group after 8 weeks of administration, but after 13 weeks of administration, the latent period of the treatment group and the positive control group were significantly shorter than the untreated control group. Initially, the SAMP8 mice showed a lower spatial exploration ability than the SAMR1 mice. However, after 13 weeks of administration, the treatment group and the control group exhibited a better exploration ability. Compared with the SAMR1 mice, the on-stage evasion time and step-down errors significantly increased in the untreated group. Compared with the untreated group, mice in the treatment group and the positive control group showed a shorter latent period after 8 weeks of administration, and the on-stage evasion time for both groups was significantly reduced after 13 weeks of administration. The treatment group showed fewer instances of electric shock. Hippocampal expression of Aß1-42 was high in the untreated group, was much lower in the positive control group, and no Aß1-42 expression was observed in the treatment group. CONCLUSIONS: The YZSH decoction improved the learning and memory of mice with AD, related to the inhibition of Aß1-42 expression.

A new insulin-sensitive enhancer from Silene viscidula, WPTS, treats type 2 diabetes by ameliorating insulin resistance, reducing dyslipidemia, and promoting proliferation of islet ß cells.

Wacao pentacyclic triterpenoid saponins (WPTS) is a newly discovered insulin sensitivity enhancer. It is a powerful hypoglycemic compound derived from Silene viscidula, which has a hypoglycemic effect similar to that of insulin. It can rapidly reduce blood glucose levels, normalizing them within 3 days of administration. However, its mechanism of action is completely different from that of insulin. Thus, we aimed to determine the pharmacological effects and mechanism of activity of WPTS on type 2 diabetes to elucidate the main reasons for its rapid effects. The results showed that WPTS could effectively improve insulin resistance in KKAy diabetic mice. Comparative transcriptomics showed that WPTS could upregulate the expression of insulin resistance-related genes such as glucose transporter type 4 (Glut4), insulin receptor substrate 1 (Irs1), Akt, and phosphoinositide 3-kinase (PI3K), and downregulate the expression of lipid metabolism-related genes such as monoacylglycerol O-acyltransferase 1 (Moat1), lipase C (Lipc), and sphingomyelin phosphodiesterase 4 (Smpd4). The results indicated that the differentially expressed genes could regulate lipid metabolism via the PI3K/AKT metabolic pathway, and it is noteworthy that WPTS was found to upregulate Glut4 expression, decrease blood glucose levels, and attenuate insulin resistance via the PI3K/AKT pathway. Q-PCR and western blotting further validated the transcriptomics findings at the mRNA and protein levels, respectively. We believe that WPTS can achieve a rapid hypoglycemic effect by improving the lipid metabolism and insulin resistance of the diabetic KKAy mice. WPTS could be a very promising candidate drug for the treatment of diabetes and deserves further research.

Therapeutic effects and mechanisms study of Hanchuan Zupa Granule in a Guinea pig model of cough variant asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or "Nai-Zi-Lai" in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases. However, the pharmacological mechanisms of HCZP remain unrevealed. AIM OF THE STUDY: To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA. MATERIALS AND METHODS: A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA. RESULTS: Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased. CONCLUSIONS: HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.

Anti-tumor and Phenotypic Regulation Effect of Matrine on Dendritic Cells through Regulating TLRs Pathway.

OBJECTIVE: To investigate the effects of matrine on antigen presentation of dendritic cells (DCs), and to explore the pharmacological mechanism of matrine on anti-tumor effect. METHODS: Different concentrations (0, 1, 2, 4, 8 and 16 µ g/mL) of matrine were co-cultured with DCs, the harvested DCs were co-cultured with antigens of Lewis lung cancer (LLC) cells, and then DCs and T cells were co-cultured to produce DCs-activated killer (DAK) cells, which have significant tumor-killing activity. The expression of cytokines, mRNA and protein of toll-like receptors (TLRs) in DCs were detected by enzyme linked immunosobent assay, polymerase chain reaction and Western blot, respectively. And the killing effect of DAK were measured by MTT assay. RESULTS: Matrine significantly increased the mRNA expression of TLR7, TLR8, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and I κ B kinase (IKK), as well as the protein expression of TLR7 and TLR8, and up-regulated the levels of interleukin-12 (IL-12), IL-6 and tumor necrosis factor-α (TNF-α), meanwhile, it also increased the expressions of MHC-II, CD54, CD80 and CD86 in DCs. DCs-activated effector T cells had significant tumor-killing activity. When the concentration of matrine was more than 4 µg/mL, all indices had significant difference (P<0.01 or P<0.05). CONCLUSION: Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway, promoting the secretion of inflammatory cytokines and enhancing immune function.

Anti-diabetic properties of genistein-chromium (III) complex in db/db diabetic mice and its sub-acute toxicity evaluation in normal mice.

BACKGROUND: In this study, chromium (III) complex was synthesized from genistein (GEN) which had good hypoglycemic activity and inorganic chromium (III) element, and its hypoglycemic activity and sub-acute toxicity were studied. METHODS: The genistein-chromium (III) complex was synthesized by chelating chromium with genistein in ethanol and its structure was determined by LC-MS, atomic absorption spectroscopy, UV-vis spectroscopy, infrared spectroscopy, elemental and thermodynamic analysis. The anti-diabetic activity of the complex was assessed in db/db mice and C57 mice by daily oral gavage for 4 weeks. The sub-acute toxicity test was carried out on KM mice with this complex. RESULTS: The molecular structure of this complex was inferred as a complex [CrGEN3] formed by three ligands and one chromium element. The complex could significantly improve the body weight of db/db mice, fasting blood glucose, random blood glucose, organ index, glycogen levels and the performance of OGTT (Oral Glucose Tolerance Test) and ITT (Insulin Tolerance Test) in db/db mice (p < 0.05). The morphology of liver, kidney, pancreas and skeletal muscle also had obviously improvement and repairment. Effects on serum indices and antioxidant enzymes activities of db/db mice showed that the serum profiles and antioxidant ability of complex group had significant improvement compared with the diabetic control group (p < 0.05 or p < 0.01), and some indices even returned to normal levels. In addition, this complex did not produce any hazardous symptoms or deaths in sub-acute toxicity test. High dose of [CrGEN3] had no significant influence on serum indices and antioxidant capacity in normal mice, and the organ tissues maintained organized and integrity in the sub-acute toxicity study. CONCLUSION: The study of the genistein-chromium (III) complex showed that the complex had good hypoglycemic activity in vivo, and did not have the potential toxicity. These results would provide an important reference for the development of functional hypoglycemic foods or pharmaceuticals.

A specific gut microbiota and metabolomic profiles shifts related to antidiabetic action: The similar and complementary antidiabetic properties of type 3 resistant starch from Canna edulis and metformin.

The relationship between gut microbiota and type 2 diabetes mellitus (T2DM) has drawn increasing attention, and the benefits of various treatment strategies, including nutrition, medication and physical exercise, maybe microbially-mediated. Metformin is a widely used hypoglycemic agent, while resistant starch (RS) is a novel dietary fiber that emerges as a nutritional strategy for metabolic disease. However, it remains unclear as to the potential degree and interactions among gut microbial communities, metabolic landscape, and the anti-diabetic effects of metformin and RS, especially for a novel type 3 resistant starch from Canna edulis (Ce-RS3). In the present study, T2DM rats were administered metformin or Ce-RS3, and the changes in gut microbiota and serum metabolic profiles were characterized using 16S-rRNA gene sequencing and metabolomics, respectively. After 11 weeks of treatment, Ce-RS3 exhibited similar anti-diabetic effects to those of metformin, including dramatically reducing blood glucose, ameliorating the response to insulin resistance and glucose tolerance test, and relieving the pathological damage in T2DM rats. Interestingly, the microbial and systemic metabolic dysbiosis in T2DM rats was effectively modulated by both Ce-RS3 and, to a lesser extent, metformin. The two treatments increased the gut bacterial diversity, and supported the restoration of SCFA-producing bacteria, thereby significantly increasing SCFAs levels. Both treatments simultaneously corrected 16 abnormal metabolites in the metabolism of lipids and amino acids, many of which are microbiome-related. PICRUSt analysis and correlation of SCFAs levels with metabolomics data revealed a strong association between gut microbial and host metabolic changes. Strikingly, Ce-RS3 exhibited better efficacy in increasing gut microbiota diversity with a peculiar enrichment of Prevotella genera. The gut microbial properties of Ce-RS3 were tightly associated with the T2DM-related indexes, showing the potential to alleviate diabetic phenotype dysbioses, and possibly explaining the greater efficiency in improving metabolic control. The beneficial effects of Ce-RS3 and metformin might derive from changes in gut microbiota through altering host-microbiota interactions with impact on the host metabolome. Given the complementarity of Ce-RS3 and metformin in regulation of gut microbiota and metabolites, this study also prompted us to suggest possible "Drug-Dietary fiber" combinations for managing T2DM.

In vitro screening and toxic mechanism exploring of leading components with potential hepatotoxicity of Herba Epimedii extracts.

Herba Epimedii is a famous Chinese edible herb, and due to its potential hepatotoxic effects, the safety associated with this herb has attracted a great deal of attention. In this study, the components of four types of the Herba Epimedii extracts were identified by HPLC-MS/MS. Among these components, 11 components that were present in all four extracts and could be obtained as reference substances were evaluated for their ability of cytotoxicity in HL-7702 and HepG2 cells, resulting in the identification of icarisid I and sagittatoside A as the most relevant with respect to the toxicity of the extracts. The targeted toxicological effects were further investigated using a series of correlated biological indicators to elucidate potentially hepatotoxic mechanisms. The results showed that the extracts and the selected compounds had varying degrees of influence on the leakage of ALT, AST and LDH; the activity of SOD, GSH and MDA; the increase in intercellular ROS; and the decrease in MMP. Among the tested substances, the ethanol extracts exhibited stronger hepatotoxicity, with icarisid I and sagittatoside A correlating with this toxic effect, and the hepatoxic mechanisms of which may be associated with damaged cell structure, increased oxidative stress and induction of apoptosis.

Research progress on Traditional Chinese Medicine syndromes of diabetes mellitus.

With the improvement of people's living standard and the changes of environment, the incidence of diabetes mellitus (DM) is on the rise day by day, while clinical treatment mainly aims at lowering blood glucose, instead of fundamental prevention and treatment. What's worse, the measures of prevention and treatment of DM complications remain inadequate. Both Chinese and modern medicine have advantages and disadvantages in treating DM, therefore, it would be a worthy attempt to break through the bottleneck of DM treatment by combining the advantages of both, and explore the new measures to prevent and deal with DM from the perspective of the combination of Traditional Chinese Medicine (TCM) syndrome and modern medicine. In this paper, modern research methods and possible indicators of TCM syndromes of DM were expounded from clinical and basic research aspects, aiming to find specific biomarkers of TCM syndromes, and providing experimental supports for the diagnosis and treatment of DM and the verification of TCM theory.

Mulberry leaf reduces inflammation and insulin resistance in type 2 diabetic mice by TLRs and insulin Signalling pathway.

BACKGROUND: It has been testified that Diabetes mellitus (DM) has a close association with chronic inflammation and Toll-like Receptors (TLRs), and DM could be prevented by mulberry leaf. Therefore, a hypothesis came into being that mulberry leaf could ameliorate proinflammation and insulin resistance (IR) through TLRs and insulin signalling pathways. METHODS: Water extracts of mulberry leaf (WEM) was given to diabetic mice by gavage for 10 weeks, and the diabetic mice was injected with low-dose streptozocin, fed with high-fat and high-sugar diet. Oral glucose tolerance tests (OGTTs) were conducted. At the same time, homeostasis model assessment of insulin (HOMA-IR) and the level of the inflammatory factor, tumour necrosis factor-α (TNF-α) was measured. The expressions of critical nodes of TLRs and insulin signalling pathway were also examined. RESULTS: WEM contributed to a significant decrease in fasting blood glucose, AUC from the investigation of OGTTs and HOMA-IR. The levels of the inflammatory factor, tumour necrosis factor-α (TNF-α) also declined. Moreover, WEM suppressed the expression of TLR2, myeloid differentiation primary-response protein 88 (MyD88), tumour-necrosis-factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-κB) in the skeletal muscle. WEM could up-regulate the expression of insulin receptor (InsR) and insulin receptor substrate 1 (IRS1), and down-regulate the phosphorylation of IRS1 in adipose tissue. CONCLUSION: Through this study, a conclusion could be made that WEM mitigates hyperglycemia, IR, and inflammation through the interactions among TLR2 signalling pathway, insulin signalling pathway and TNF-α.

Effect of 2″-O-Rhamnosyl Icariside II, Baohuoside I and Baohuoside II in Herba Epimedii on Cytotoxicity Indices in HL-7702 and HepG2 Cells.

Herba Epimedii, a commonly used Chinese medicine, has attracted much attention recently because of its potential hepatotoxic effects. 2″-O-Rhamnosyl icariside II, baohuoside I and baohuoside II are the main components of Herba Epimedii, and previous research indicates that these three compounds are related to the hepatotoxicity of Herba Epimedii. To test this idea, in this study, HL-7702 and HepG2 cells were chosen as the in vitro models and the influences of these three compounds on a series of cytotoxicity indices, including ALT, AST, LDH, SOD, GSH, MDA, ROS and MMP, were determined. The results showed that at certain concentrations, the three compounds had different effects on the indices. Among them, baohuoside I at high concentration (32 µg/mL) displayed more significant cytotoxicity than the other two compounds; therefore, it was inferred to be more closely correlated with the liver injury induced by Herba Epimedii combined with the previous study, and its toxic mechanisms may be involved in increasing oxidative stress and inducing apoptosis. The findings of this study may provide evidence of the toxic composition of Herba Epimedii to preliminarily discuss the toxic mechanisms and provide improved guidance for its clinical safety.

Subchronic Toxicity Studies of Cortex Dictamni Extracts in Mice and Its Potential Hepatotoxicity Mechanisms in Vitro.

Cortex Dictamni is a commonly-used traditional Chinese herbal medicine for the treatment of skin inflammation, tinea, and eczema. Recently, some studies reported that Cortex Dictamni might induce liver injury, suggesting more attention to its safety. The current study was designed to investigate subchronic toxicity of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDEE) in mice and the potential hepatotoxicity mechanisms in vitro. Firstly, CDAE or CDEE groups were administrated with varying dosages (2.3, 4.6, or 9.2 g/kg/day, p.o.) in mice for 28 days in subchronic toxicity studies. General clinical signs and biochemical parameters were examined, and morphological analyses were conducted. Secondly, we identified the different constituents of CDAE and CDEE using HPLC-MS/MS and chose major components for further study. In order to determine the toxic components, we investigated the cytotoxicity of extracts and chosen components using CCK-8 assay in HepG2 cells. Furthermore, we explored the possible hepatotoxicity mechanisms of Cortex Dictamni using a high content analysis (HCA). The results showed that no significant differences of general clinical signs were observed in mice. Aspartate alanine aminotransferase (ALT) and aminotransferase (AST) were significantly increased in the high-dose CDAE and CDEE groups compared to the control group. Meanwhile, the absolute and relative liver weights and liver/brain ratio were significantly elevated, and histological examination of liver demonstrated cellular enlargement or nuclear shrinkage. In UPLC analysis, we compared the chemical constituents between CDAE and CDEE, and chose dictamnine, obakunone, and fraxinellone for hepatotoxicity evaluation in the in vitro studies. In the CCK-8 assay, CDAE, CDEE, dictamnine, obakunone, and fraxinellone decreased the cell viability in a dose-dependent manner after treatment for 48 h. Furthermore, the cell number decreased, while the nuclear intensity, cell membrane permeability, and concentration of reactive oxygen species were shown to increase, meanwhile, mitochondrial membrane potential was also changed in HepG2 cells following 48 h of compounds treatment using HCA. Our studies suggested that CDAE and CDEE have potential hepatotoxicity, and that the alcohol extraction process could increase toxicity. Dictamnine, obakunone, and fraxinellone may be the possible toxic components in Cortex Dictamni with dictamnine as the most potentially hepatotoxic component, whose potential hepatotoxicity mechanism may be associated with cell apoptosis. Moreover, this study could provide valuable data for clinical drug safety research of Cortex Dictamni and a good example for safety study of other Chinese herbal medicines.

UPLC-HRMS-Based Plasma Metabolomic Profiling of Novel Biomarkers by Treatment with KDZI in Cerebral Ischemia Reperfusion Rats.

Kudiezi injection (KDZI), also known as Diemailing injection, is a traditional Chinese medicine injection of the composite plant Ixeris sonchifolia Hance (also known as Kudiezi), and has been widely used to treat coronary heart disease, angina pectoris, and cerebral infarction, but its pharmacological mechanisms remain unclear. This study is designed to explore the effects of KDZI on middle cerebral artery occlusion and reperfusion (MCAO/R) rats, and to identify metabolic features of cerebral ischemia reperfusion by using a nontargeted metabolic profiling method based on ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). In this process, 32 potential biomarkers were found in plasma. KDZI significantly upregulated the levels of taurochenodesoxycholic acid, leucine, l-phenylalanine, l-tryptophan, arachidonic acid (ARA), and phosphatidyl ethanolamines (PE), phosphatidyl cholines (PC) and downregulated the levels of l-valine and 5-hydroxyindole-3-acetic acid (5-HIAA) in plasma. The results indicated that the mechanisms of KDZI on MCAO/R were related to the mechanisms of amino acid and lipid metabolism.

Tissue metabolomics study to reveal the toxicity of a traditional Tibetan medicine 'Renqing Changjue' in rats.

Renqing Changjue (RQCJ), a precious Traditional Tibetan Medicine (TTM), has been widely used in the management of diseases of the digestive system, toxinosis and pyreticosis. However, in the formula, a significant level of heavy metals, which are potential toxic elements, are present. Therefore, it is important to assess the toxicity of RQCJ dynamically and holistically. In the present study, a 1H NMR metabolomics approach and inductively coupled plasma mass spectrometry (ICP-MS) were implemented to analyze the samples of liver, kidney and spleen from rats treated with RQCJ. The results revealed that 9 metabolites in the liver, 13 metabolites in the kidney and 16 metabolites in the spleen were significantly altered, which suggest that disturbances in TCA cycle, amino acid metabolism, energy metabolism and oxidative stress are produced by successive administration of RQCJ over 15 days. Complemented by histopathology and biochemical assay, the trends of the metabolite levels indicate that RQCJ caused tissue injury to a certain extent, which was evidenced by the high levels of As and Hg in the tissue. The toxic effects of RQCJ were alleviated in liver and kidney during the recovery period, and RQCJ may cause long-term damage in spleen. These findings provide a significant experimental proof on the estimated safety and valuable information about the metabolism of RQCJ, which will be valuable in determining the health risks of the drug.

Screening and Identification of the Metabolites in Rat Plasma and Urine after Oral Administration of Areca catechu L. Nut Extract by Ultra-High-Pressure Liquid Chromatography Coupled with Linear Ion Trap-Orbitrap Tandem Mass Spectrometry.

Areca catechu L. nut, a well-known toxic traditional herbal medicine, has been widely used to treat various diseases in China and many other Asian countries for centuries. However, to date the in vivo absorption and metabolism of its multiple bioactive or toxic components still remain unclear. In this study, liquid chromatography coupled with tandem mass spectrometry was used to analyze the major components and their metabolites in rat plasma and urine after oral administration of Areca catechu L. nut extract (ACNE). A total of 12 compounds, including 6 alkaloids, 3 tannins and 3 amino acids, were confirmed or tentatively identified from ACNE. In vivo, 40 constituents, including 8 prototypes and 32 metabolites were identified in rat plasma and urine samples. In summary, this study showed an insight into the metabolism of ACNE in vivo, which may provide helpful chemical information for better understanding of the toxicological and pharmacological profiles of ACNE.